McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Tissue Eng Part A. 2011 Dec;17(23-24):3033-44. doi: 10.1089/ten.TEA.2011.0257. Epub 2011 Aug 29.
Biologic scaffolds composed of extracellular matrix (ECM) have been used successfully in preclinical models and humans for constructive remodeling of functional, site-appropriate tissue after injury. The mechanisms underlying ECM-mediated constructive remodeling are not completely understood, but scaffold degradation and site-directed recruitment of progenitor cells are thought to play critical roles. Previous studies have identified a cryptic peptide derived from the C-terminal telopeptide of collagen IIIα that has chemotactic activity for progenitor cells. The present study characterized the osteogenic activity of the same peptide in vitro and in vivo in an adult murine model of digit amputation. The present study showed that the cryptic peptide increased calcium deposition, alkaline phosphatase activity, and osteogenic gene expression in human perivascular stem cells in vitro. Treatment with the cryptic peptide in a murine model of mid-second phalanx digit amputation led to the formation of a bone nodule at the site of amputation. In addition to potential therapeutic implications for the treatment of bone injuries and facilitation of reconstructive surgical procedures, cryptic peptides with the ability to alter stem cell recruitment and differentiation at a site of injury may serve as powerful new tools for influencing stem cell fate in the local injury microenvironment.
生物支架由细胞外基质 (ECM) 组成，已成功应用于临床前模型和人体，用于损伤后功能性、合适部位组织的建设性重塑。ECM 介导的建设性重塑的机制尚不完全清楚，但支架降解和定向募集祖细胞被认为起着关键作用。先前的研究已经确定了一种源自胶原 IIIα 末端短肽的隐藏肽，该肽对祖细胞具有趋化活性。本研究在成人断指模型中，从体外和体内两个方面研究了该相同肽的成骨活性。本研究表明，该隐藏肽可增加人血管周干细胞的钙沉积、碱性磷酸酶活性和成骨基因表达。在中间第二节指骨断指的小鼠模型中用该隐藏肽治疗，导致在断指部位形成骨结节。除了对治疗骨损伤和促进重建手术程序具有潜在的治疗意义外，具有改变损伤部位干细胞募集和分化能力的隐藏肽可能成为影响局部损伤微环境中干细胞命运的强大新工具。
